Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) play a central role in the management of brain metastases, allowing the delivery of biologically ablative doses to well-defined target volumes with a rapid dose gradient and sparing of healthy parenchyma. However, cerebral radionecrosis (RN) is among the most significant late complications, with an incidence of 4-30%. It is a radiation-induced injury characterized by obliterative vasculopathy, hypoxia, dysfunctional neoangiogenesis (VEGF-mediated), massive vasogenic edema, and neuroinflammation. Clinically and neuroradiologically, RN closely mimics tumor recurrence or progression, making the differential diagnosis via Magnetic Resonance Imaging (MRI) and complementary methods a complex challenge. An experimental, observational, retrospective epidemiological study was conducted on an initial cohort of 32 patients (median age 61 years; 78% males, 22% females) with brain metastases, consecutively treated between 2020 and 2022 at the AOU Ospedali Riuniti Marche Nord (Pesaro and Fano facilities) using hypofractionated SRT in 3 or 5 sessions. Three subjects were excluded from the study, resulting in a total of 29 patients who were monitored using 1.5T MRI scanners (Philips Ingenia and GE Voyager), primarily in three phases (pre-treatment, first follow-up, and last follow-up), whereas radionecrosis cases were evaluated throughout their entire follow-up pathway. The neuroradiological criteria adopted for the diagnosis of RN included: disproportion of vasogenic edema compared to the enhancing lesion on T1-weighted images, presence of a T1/T2 mismatch, central diffusion restriction on DWI/ADC, and hypoperfusion (reduced rCBV) with a decreased Cho/NAA ratio where DSC perfusion and spectroscopy (MRS) were available. In the analyzed cohort, 5 patients (16.1%) developed radionecrosis (3 symptomatic G2 cases and 2 asymptomatic G1 cases according to CTCAE grading), with an onset ranging between 7 and 24 months post-treatment. All 5 patients had received primary SRT of 27 Gy in 3 fractions (9 Gy/fx), and 80% (4/5) were receiving concurrent and/or sequential next-generation systemic therapy. Dosimetrically, the mean GTV and PTV volumes in RN cases were 3.62 ± 2.52 cm³ and 9.15 ± 4.71 cm³, respectively, with a mean V20Gy of 19.83 ± 7.51 cm³ and a mean Brain Dose of 246.9 ± 116.5 cGy. In our study, the observed incidence of radionecrosis (16.1%) and the local control rate (81%) are fully consistent with literature data. Diagnostically, the study primarily relied on the analysis of conventional sequences, to which functional and metabolic sequences were added. Image reprocessing via workstation with the assessment of the T1/T2 mismatch can provide a significant contribution. The time factor is another crucial element for an accurate diagnosis. The role of the Medical Radiology Technician (TSRM) is central to the correct and comprehensive acquisition of an MRI study during the follow-up of a patient treated for brain metastases.
La radiochirurgia stereotassica (SRS) e la radioterapia stereotassica frazionata (SRT) rivestono un ruolo centrale nella gestione delle metastasi encefaliche, consentendo di erogare dosi biologicamente ablative a volumi bersaglio circoscritti con un rapido gradiente di dose e risparmio del parenchima sano. Tuttavia, tra le complicanze tardive più rilevanti figura la radionecrosi (RN) cerebrale con incidenza del 4-30%, un danno radio-indotto caratterizzato da vasculopatia obliterativa, ipossia, neoangiogenesi disfunzionale (mediata da VEGF), massiccio edema vasogenico e neuroinfiammazione. Sul piano clinico e neuroradiologico, la RN simula fedelmente una recidiva o progressione tumorale, rendendo la diagnosi differenziale tramite Risonanza Magnetica (RM) e metodiche complementari una sfida complessa. È stato condotto uno studio epidemiologico retrospettivo osservazionale sperimentale su una coorte iniziale di 32 pazienti (età mediana 61 anni; 78% maschi, 22% femmine) affetti da metastasi cerebrali e trattati consecutivamente tra il 2020 e il 2022 presso l'AOU Ospedali Riuniti Marche Nord (presidi di Pesaro e Fano) con tecnica SRT ipofrazionata in 3 o 5 sedute. I soggetti esclusi dallo studio sono stati 3 per un totale di 29 pazienti che sono stati monitorati su apparecchiature RM da 1.5T (Philips Ingenia e GE Voyager), principalmente in tre fasi (pre-trattamento, primo controllo, ultimo follow-up), mentre i casi di radionecrosi sono stati valutati in tutto il loro percorso di controllo. I criteri neuroradiologici adottati per la diagnosi di RN hanno incluso: sproporzione dell'edema vasogenico rispetto alla lesione captante in T1, presenza di T1/T2 mismatch, restrizione centrale della diffusione in DWI/ADC ed ipoperfusione (ridotto rCBV) con riduzione del rapporto Cho/NAA ove disponibili perfusione DSC e spettroscopia (MRS). Nella coorte analizzata, 5 pazienti (16,1%) hanno sviluppato radionecrosi (3 casi sintomatici di grado G2 e 2 casi asintomatici G1 secondo grading CTCAE), con un'insorgenza compresa tra 7 e 24 mesi dal trattamento. Tutti i 5 pazienti avevano ricevuto una SRT primaria di 27 Gy in 3 frazioni (9 Gy/fx) e l'80% (4/5) assumeva terapia sistemica concomitante e/o sequenziale di nuova generazione. Dal punto di vista dosimetrico, il volume medio di GTV e PTV nei casi di RN è risultato rispettivamente di 3,62 ± 2,52 cm3 e 9,15 ± 4,71 cm3, con un V20Gy medio di 19,83 ± 7,51cm3 e una Brain Dose media di 246,9 ± 116,5cGy. Nel nostro lavoro l’incidenza di radionecrosi (16,1%), il tasso di controllo locale (81%) osservati risultano pienamente in linea con i dati della letteratura. Dal punto di vista diagnostico, lo studio si è basato principalmente sull’analisi di sequenze di tipo convenzionale alla quale aggiungere sequenze funzionali e metaboliche. La riebolazione attraverso Workstation delle immagini con la valutazione del mismatch T1/T2 può fornire un contributo rilevante. Il fattore tempo è un altro elemento determinante ai fini di un’accurata diagnosi. Il ruolo del TSRM (Tecnico Sanitario di Radiologia Medica) è centrale nella corretta ed esaustiva acquisizione di uno studio RM nel follow-up del paziente trattato per metastasi cerebrale
I DUE VOLTI DELLA RADIOTERAPIA STEREOTASSICA. NELLA LUCE E NELL’OMBRA DEL TRATTAMENTO DI LESIONI CEREBRALI
COACCI, FRANCESCO
2025/2026
Abstract
Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) play a central role in the management of brain metastases, allowing the delivery of biologically ablative doses to well-defined target volumes with a rapid dose gradient and sparing of healthy parenchyma. However, cerebral radionecrosis (RN) is among the most significant late complications, with an incidence of 4-30%. It is a radiation-induced injury characterized by obliterative vasculopathy, hypoxia, dysfunctional neoangiogenesis (VEGF-mediated), massive vasogenic edema, and neuroinflammation. Clinically and neuroradiologically, RN closely mimics tumor recurrence or progression, making the differential diagnosis via Magnetic Resonance Imaging (MRI) and complementary methods a complex challenge. An experimental, observational, retrospective epidemiological study was conducted on an initial cohort of 32 patients (median age 61 years; 78% males, 22% females) with brain metastases, consecutively treated between 2020 and 2022 at the AOU Ospedali Riuniti Marche Nord (Pesaro and Fano facilities) using hypofractionated SRT in 3 or 5 sessions. Three subjects were excluded from the study, resulting in a total of 29 patients who were monitored using 1.5T MRI scanners (Philips Ingenia and GE Voyager), primarily in three phases (pre-treatment, first follow-up, and last follow-up), whereas radionecrosis cases were evaluated throughout their entire follow-up pathway. The neuroradiological criteria adopted for the diagnosis of RN included: disproportion of vasogenic edema compared to the enhancing lesion on T1-weighted images, presence of a T1/T2 mismatch, central diffusion restriction on DWI/ADC, and hypoperfusion (reduced rCBV) with a decreased Cho/NAA ratio where DSC perfusion and spectroscopy (MRS) were available. In the analyzed cohort, 5 patients (16.1%) developed radionecrosis (3 symptomatic G2 cases and 2 asymptomatic G1 cases according to CTCAE grading), with an onset ranging between 7 and 24 months post-treatment. All 5 patients had received primary SRT of 27 Gy in 3 fractions (9 Gy/fx), and 80% (4/5) were receiving concurrent and/or sequential next-generation systemic therapy. Dosimetrically, the mean GTV and PTV volumes in RN cases were 3.62 ± 2.52 cm³ and 9.15 ± 4.71 cm³, respectively, with a mean V20Gy of 19.83 ± 7.51 cm³ and a mean Brain Dose of 246.9 ± 116.5 cGy. In our study, the observed incidence of radionecrosis (16.1%) and the local control rate (81%) are fully consistent with literature data. Diagnostically, the study primarily relied on the analysis of conventional sequences, to which functional and metabolic sequences were added. Image reprocessing via workstation with the assessment of the T1/T2 mismatch can provide a significant contribution. The time factor is another crucial element for an accurate diagnosis. The role of the Medical Radiology Technician (TSRM) is central to the correct and comprehensive acquisition of an MRI study during the follow-up of a patient treated for brain metastases.| File | Dimensione | Formato | |
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tesi laurea coacci.pdf
embargo fino al 05/05/2028
Descrizione: Tesi di laurea Francesco Coacci
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5.82 MB | Adobe PDF |
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https://hdl.handle.net/20.500.12075/29827